Interaction of a Neutral Endopeptidase Inhibitor with an ANP-C Receptor Ligand in Anesthetized Dogs

Inhibition of important degradative pathways of atrial natriuretic peptide (ANP) in vivo could be a valuable therapeutic tool for regulating endogenous levels of ANP. The aim was to investigate the in vivo effects of both blockade of atrial natriuretic peptide clearance receptor and inhibition of neutral endopeptidase 24.11, an enzyme shown to be involved in ANP breakdown. Therefore, we infused a specific neutral endopeptidase inhibitor ((S)-thiorphan) and an ANP-C receptor ligand (AP 811) alone or in combination into anaesthetized beagle dogs.

Compared with vehicle controls, coadministration of (S)-thiorphan and AP 811 (100μg/kg/min and 10μg/kg/min, resp.) had greater effects on endocrine and renal parameters than administration of either substance alone.